DESCRIPTION: (Principal Investigator's Abstract) The aims of this work are to develop new methods for organic synthesis. In particular, methods to effect the reduction of prochiral functional groups and to effect carbon-carbon bond formation are proposed. The development of new synthetic methods is of central importance to the development of organic synthesis, in particular, and organic chemistry in general. The availability of general and predictable means by which to assemble large numbers of small molecules in both a specific, as well as a combinatorial fashion is key to the uncovering of new lead structures in drug discovery. Moreover, the ability to quickly generate a diverse set of analogs of the initial lead compounds is essential for the rapid arrival at compounds with improved pharmacological profiles. In recent years, a growing emphasis on the preparation of single enantiomer compounds as pharmaceutical agents has prompted intensive activity in the area of asymmetric synthesis. Asymmetric catalysis offers a particularly efficient means to enhance access to pharmaceutical agents of a single "handedness." Many of the applications described in this proposal, including the preparation of enantiomerically pure amines, biaryls and cycloalkones could have an immediate impact on the efficient access to a variety of important molecules, be they lead compounds in drug discovery, or analogs of the initial leads that possess a better pharmacological profile.